DK143276B - METHOD OF ANALOGUE FOR THE PREPARATION OF N-BETA-SUBSTITUTED 8-BETA-AMINOETHYLERGOLINE-I DERIVATIVES AND SALTS THEREOF - Google Patents
METHOD OF ANALOGUE FOR THE PREPARATION OF N-BETA-SUBSTITUTED 8-BETA-AMINOETHYLERGOLINE-I DERIVATIVES AND SALTS THEREOF Download PDFInfo
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- DK143276B DK143276B DK326475AA DK326475A DK143276B DK 143276 B DK143276 B DK 143276B DK 326475A A DK326475A A DK 326475AA DK 326475 A DK326475 A DK 326475A DK 143276 B DK143276 B DK 143276B
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- Prior art keywords
- aminoethylergoline
- beta
- general formula
- methyl
- substituted
- Prior art date
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(φ) (19) DANMARK \Ra/(φ) (19) DENMARK \ Ra /
|j| (12) FREMUEGGELSESSKRIFT od 143276 B| J | (12) PROCEDURE WRITING OR 143276 B
Dl REKTORATET FOR PATENT- OG VAREMÆRKEVÆSENETDl The Patent and Trademark Office
(21) Ansøgning nr. 3264/75 (61) IntCI* C 07 D 457/02 (22) Indleveringsdag 17- jul. 1975 (24) Løbedag 17. jul. 1975 (41) Aim. tilgængelig 20. jan. 1976 (44) Fremlagt 3« aug. 1981 (86) International ansøgning nr. - (86) International indleveringsdag - (85) Videreførelsesdag - (62) Stamansøgning nr. -(21) Application No. 3264/75 (61) IntCI * C 07 D 457/02 (22) Filing day 17-Jul. 1975 (24) Race day 17 Jul. 1975 (41) Aim. available Jan 20 1976 (44) Presented 3 «Aug. 1981 (86) International Application No. - (86) International Filing Day - (85) Continuation Day - (62) Master Application No. -
(30) Prioritet 19· Jul. 1974, 5178/74, CS(30) Priority 19 · Jul. 1974, 5178/74, CS
(71) Ansøger SPOFA SPOJENE PODNIKY PRO ZDRåVOTNICKOU VYROBU, Praha 5, CS.(71) Applicant SPOFA SPOJENE PODNIKY PRO ZDRåVOTNICKOU VYROBU, Praha 5, CS.
(72) Opfinder Miroslav _Semonsky, CS: Antonin _Cerny, CS: Marie Krajcro® va, CS: Karel Rezabek, CS: Marie Auskova, CS: ra. fl.(72) Inventor Miroslav _Semonsky, CS: Antonin _Cerny, CS: Marie Krajcro® va, CS: Karel Rezabek, CS: Marie Auskova, CS: ra. fl.
(74) Fuldmægtig Firmaet Chas. Rude.(74) Associate Company Chas. Rude.
(54) Analogifremgangsmåde til fremstil® ling af N-beta-substituerede 8-be= t a-amino ethyler go lin-I-d erivat er og salte deraf.(54) Analogous procedure for the preparation of N-beta-substituted 8-beta-α-amino ethyler goin-I-d derivative and its salts.
Opfindelsen angår en analogifremgangsmåde til fremstilling af hidtil ukendte 'Ν-β-substituerede 8-S-aminoethylergolin-I-derivater med den almene formel I 1 CQ CHpCHpN^ S ^The invention relates to an analogous process for the preparation of novel β-β-substituted 8-S-aminoethylergoline-I derivatives of the general formula I C
CMCM
COCO
J· (I) *J (I) *
r5_h-- 2 143276 hvori R1 betegner isopropylgruppen eller 1-methylpropylgruppen, og R betegner et hydrogenatom eller methylgruppen, eller forbindelsernes farmaceutisk acceptable additionssalte med uorganiske eller organiske syrer.r5_h-- 2 143276 wherein R 1 represents the isopropyl group or 1-methylpropyl group and R represents a hydrogen atom or the methyl group or the pharmaceutically acceptable addition salts of inorganic or organic acids.
Fremgangsmåden ifølge opfindelsen til fremstilling af N-3-substituere-de 8-3-aminoethylergolin-I-derivater er karakteriseret ved, at manThe process of the invention for the preparation of N-3-substituted 8-3-aminoethylergoline-I derivatives is characterized in that:
omsætter β-aminoethylergoliner-I med den almene formel IIreacting β-aminoethylergolines-I of the general formula II
ch2ch2nh2 lj-CH3 ^ (II) R5-N---ch2ch2nh2 lj-CH3 ^ (II) R5-N ---
hvori Ir har den ovenfor anførte betydning, med en keton med den almene formel IIIwherein Ir has the meaning set forth above, with a ketone of the general formula III
s'*" C0. (III) \Ch3 hvori R4 betegner methyl- eller ethylgruppen, hvorefter man hydrogenerer det dannede mellemprodukt med hydrogen i nærværelse af en katalysator og derefter eventuelt omdanner den rå base med den almene formel I til et syreadditionssalt med en organisk eller u-organisk syre.wherein R 4 represents the methyl or ethyl group, then hydrogenates the formed intermediate with hydrogen in the presence of a catalyst and then optionally converts the crude base of the general formula I into an acid addition salt with an organic or inorganic acid.
143276 3143276 3
Den reduktive alkylering gennemfører man ved hydrogenering af en blanding af aminoforbindelsen med den almene formel II og 1-3 molækvivalenter af en keton med den almene formel III i et passende opløsningsmiddel og i nærværelse af en katalysator med hydrogen ved et tryk på 1 til 70 atm og ved temperaturer fra 10 til 140°C. I de fleste tilfælde gennemfører man hydrogeneringen under et moderat vandtryk på 70-00 mm vandsøjle ved temperaturer på 20-5Q°C. Som katalysator kan anvendes sædvanlige hydrogeneringskatalysatorer, eksempelvis palladium, platin eller Raney-nikkel, eventuelt på passende bærere. Som opløsningsmiddel kan anvendes alkoholer, såsom methanol, ethanol, propanol, isopropanol og lignende, ethere, såsom tetrahydrofuran eller dioxan, og blandinger af passende opløsningsmidler med vand. Ketonerne tilsættes hensigtsmæssigt i et moderat overskud, fortrinsvis i en mængde på 1,1 til 1,5 molækvivalenter, regnet i forhold til 1 molækvivalent af aminoforbindelsen med den almene formel II.The reductive alkylation is carried out by hydrogenating a mixture of the amino compound of the general formula II and 1-3 molar equivalents of a ketone of the general formula III in a suitable solvent and in the presence of a catalyst with hydrogen at a pressure of 1 to 70 atm. and at temperatures of 10 to 140 ° C. In most cases, hydrogenation is carried out under a moderate water pressure of 70-00 mm water column at temperatures of 20-5Q ° C. As the catalyst, conventional hydrogenation catalysts, for example palladium, platinum or Raney nickel, may be used, optionally on suitable carriers. As the solvent may be used alcohols such as methanol, ethanol, propanol, isopropanol and the like, ethers such as tetrahydrofuran or dioxane, and mixtures of suitable solvents with water. The ketones are conveniently added in a moderate excess, preferably in an amount of 1.1 to 1.5 molar equivalents, calculated from 1 molar equivalent of the amino compound of the general formula II.
Pra reaktionsblandingen efter den reduktive alkylering isolerer man efter frafiltrering af katalysatoren og efter afdampning af opløsningsmidlet aminoforbindelserne med den almene formel I ved krystallisation og/eller søjlekromatografi, eller således, at man til at begynde med omdanner den rå base med den almene formel I til et passende additionssalt med en organisk eller uorganisk syre og derpå renser forbindelsen i form af dettes salt.After the reductive alkylation, the reaction mixture is isolated, after filtration of the catalyst and after evaporation of the solvent, the amino compounds of the general formula I by crystallization and / or column chromatography, or so as to initially convert the crude base of the general formula I to a appropriate addition salt with an organic or inorganic acid and then purifies the compound in the form of its salt.
De som udgangsmateriale tjenende 8-(3-aminoethylergoliner kendes fra tjekkoslovakisk forfattercertifikat nr. 171.480.The starting material 8- (3-aminoethylergolines) is known from Czechoslovakian author's certificate No. 171,480.
De farmaceutisk acceptable syreadditionssalte af forbindelserne med den almene formel I fremstilles ved indvirkning af 1-3 molækvivalenter af en organisk eller uorganisk syre på 1 molækvivalønt af basen med den almene formel I i et passende opløsningsmiddel, fortrinsvis i methanol, ethanol, vand eller blandinger deraf. Som egnet syre kan eksempelvis anvendes svovlsyre, saltsyre, hydrogenbro= midsyre, methansulfonsyre, vinsyre, maleinsyre etc. Særlig fordelagtige er bishydrogenmaleinaterne af forbindelserne med den almene formel I, som krystalliserer godt fra alkoholer og desuden er letop-løselige i vand, således at de er velegnede til oral og parenteral anvendelse.The pharmaceutically acceptable acid addition salts of the compounds of the general formula I are prepared by the action of 1-3 molar equivalents of an organic or inorganic acid of 1 molar equivalent of the base of the general formula I in a suitable solvent, preferably in methanol, ethanol, water or mixtures thereof. . As suitable acid can be used, for example, sulfuric acid, hydrochloric acid, hydrobromic acid, methanesulfonic acid, tartaric acid, maleic acid etc. Particularly advantageous are the bishydrogen malinates of the compounds of the general formula I which crystallize well from alcohols and are also readily soluble in water. are suitable for oral and parenteral use.
44
14327G14327G
Forbindelserne med den almene formel I og deres farmaceutisk acceptable salte, der er forholdsvis lidt toksiske, har betydningsfulde farmakologiske virkninger, som kan udnyttes i human- og veterinærterapien og til påvirkning af forskellige patologiske og fysiologiske tilstande. I første række er forbindelserne virksomme inhibitorer af prolaktinsekretionen i adenohypofysen samt stimulatorer af gonado-trophinsekretionen i den nævnte kirtel. I måleffekten giver den pro-laktininhiberende virkning sig eksempelvis udslag som antinidations-eller antilaktationsvirkning, den stimulerende virkning på gonado-trophinsekretionen som evne til at fremkalde oestrus. Den med inhi-beringen af prolaktinsekretionen forbundne måleffekt kan atter ophæves ved tilførsel af eksogent prolaktin. Forbindelserne med den almene formel I nedsætter ligeledes i ikke-toksiske mængder prosta-tavægten hos forsøgsdyr, f.eks. rotter.The compounds of general formula I and their pharmaceutically acceptable salts, which are relatively toxic, have significant pharmacological effects which can be utilized in human and veterinary therapy and to influence various pathological and physiological conditions. First, the compounds are effective inhibitors of the prolactin secretion in the adenohypophysis as well as stimulators of the gonadotrophin secretion in said gland. For example, in the measuring effect, the pro-lactin inhibitory effect results in effects such as antinidation or anti-lactation effect, the stimulating effect on the gonadotrophin secretion as the ability to induce oestrus. The measurement effect associated with the inhibition of prolactin secretion can again be abrogated by the application of exogenous prolactin. The compounds of general formula I also reduce in non-toxic amounts the prostate weight of test animals, e.g. rats.
Sammenligning af antilaktationsvirkningen af nogle D-6-methyl-8-(3-alkylaminoethylergoliner-IComparison of the anti-lactation effect of some D-6-methyl-8- (3-alkylaminoethylergolines-I
Forbindelse Antilaktationsvirkning (1) ED50 (mg/kg) Vægtforøgelse Mælkepletter D-6-methyl-8-p-isopropyl= aminoethylergolin-I (2) 0,12 p.o. 0,06 p.o.Compound Antifacting effect (1) ED50 (mg / kg) Weight gain Milk spots D-6-methyl-8-p-isopropyl = aminoethylergoline-I (2) 0.12 p.o. 0.06 p.o.
D-6-methyl-8-p-(1-methylpropyl)- aminoethylergolin-I (2) " 0,20 p.o. 0,10 p.o.D-6-methyl-8-p- (1-methylpropyl) aminoethylergoline-I (2) "0.20 p.o. 0.10 p.o.
D-6-methyl-8-ergolin-I- yleddikesyreamid (3) 0,22 p.o. 0,15 p.o.D-6-methyl-8-ergolin-I-yl acetic acid amide (3) 0.22 p.o. 0.15 p.o.
D-6-methyl-8-cyanmethyl= ergolin-I (4) 0,79 p.o. 0,74 p.o.D-6-methyl-8-cyanomethyl = ergoline-I (4) 0.79 p.o. 0.74 p.o.
'2-brom-a-ergocryptin (5) 3,5 s.c.2-Bromo-a-ergocryptin (5) 3.5 s.c.
(1) Virkningen af de afprøvede stoffer blev undersøgt på diende Wistar-rotter ved hjælp af standardmetoden ifølge E. Fluckiger og H.R. Wagner, Experientia 24, 1130 (1968), dels i henseende til vægtforøgelsen hos de diende dyr i sammenligning med kontroldyr, dels ved bedømmelse af de såkaldte "mælkepletter", hvis størrelse svarer til fyldningsgraden af dyrenes maver med mælk.(1) The effect of the tested substances was investigated on Wistar rats using the standard method of E. Fluckiger and H.R. Wagner, Experientia 24, 1130 (1968), partly in relation to the weight gain of the animals in comparison with control animals, and partly in the assessment of the so-called "milk spots", the size of which corresponds to the degree of filling of the animals' stomachs with milk.
(2) En ifølge opfindelsen fremstillet forbindelse med den almene formel I.(2) A compound of the general formula I prepared according to the invention
(3) Den mest virksomme forbindelse, som kendes fra svensk fremlæggelsesskrift nr. 381.875.(3) The most effective connection known from Swedish Patent Publication No. 381,875.
14327 G14327 G
5 (4) En til sammenligning anført kendt forbindelse (Semonsk^ M., Kucharczyk N., Collection Czechoslov.Chem.Commun. 33, 577 (1968)), dansk patentskrift nr. 124.080.5 (4) A known compound for comparison (Semonsk ^ M., Kucharczyk N., Collection Czechoslov.Chem.Commun. 33, 577 (1968)), Danish Patent No. 124,080.
(5) E. Fluckiger, H.R. Wagner, Experientia 24, 1130 (1968) - den kendte prolaktininhiberende sammenligningsforbindelse.(5) E. Fluckiger, H.R. Wagner, Experientia 24, 1130 (1968) - the known prolactin inhibitory comparison compound.
Eksempel 1 D-6-methyl-8-P-isopropylaminoethylergolin-I.Example 1 D-6-methyl-8-β-isopropylaminoethylergoline-I.
Til en opløsning af 1,35 g (5 mmol) D-6-methyl-8-p-aminoethylergo= lin-I i 75 ml ethanol sættes 0,32 g (5,5 mmol) acetone og 75 mg katalysator ifølge Adams, og blandingen hydrogeneres under rystning og opvarmning til ca. 40°C med hydrogen under et tryk på ca. 80 cm vandsøjle. Efter ca. 5 timers hydrogenering er den teoretiske hy= drogenmængde (135 ml) forbrugt. Hydrogeneringen afbrydes, katalysatoren frafiltreres, og opløsningsmidlet afdampes vinder formindsket tryk indtil tørhed, hvorefter resten renses (udbytte 1,6 g, praktisk talt 100$) ved omkrystallisation fra en acetone-hexan-blanding (1:5). Man opnår D-6-methyl-8^-isopropylaminoethylergolin-I med smeltepunkt 105-107°C, [<x]p° = -95° (c = 0,5, pyridin).To a solution of 1.35 g (5 mmol) of D-6-methyl-8-p-aminoethylergo-lin-I in 75 ml of ethanol is added 0.32 g (5.5 mmol) of acetone and 75 mg of catalyst according to Adams, and the mixture is hydrogenated with shaking and heating to ca. 40 ° C with hydrogen under a pressure of approx. 80 cm water column. After approx. 5 hours of hydrogenation, the theoretical amount of hydrogen (135 ml) is consumed. The hydrogenation is quenched, the catalyst is filtered off and the solvent evaporated decreases to reduced pressure until dryness, then the residue is purified (yield 1.6 g, practically $ 100) by recrystallization from an acetone-hexane mixture (1: 5). D-6-methyl-8β-isopropylaminoethylergoline-I is obtained, mp 105-107 ° C, [<x] p ° = -95 ° (c = 0.5, pyridine).
Bishydrogenmaleinatet af den opnåede base kan f.eks. fremstilles ved, at man til en opløsning af 0,31 g D-6-methyl-8^-isopropylaminoethyl= ergolin-I i 2 il methanol sætter en opløsning af 0,232 g maleinsyre i 1 ml methanol, frafiltrerer det udskilte salt og omkrystalliserer fra ethanol. Udbytte 0,45 g med smeltepunkt 166-167°C (under dekom-ponering), [a]^0 = -38,5° (c = 0,5, vand).The bishydrogen malinate of the base obtained can e.g. is prepared by adding to a solution of 0.31 g of D-6-methyl-8β-isopropylaminoethyl = ergoline-I in 2 µl of methanol a solution of 0.232 g of maleic acid in 1 ml of methanol, filtering off the separated salt and recrystallizing from ethanol. Yield 0.45 g, m.p. 166-167 ° C (with decomposition), [α] 20 = -38.5 ° (c = 0.5, water).
Eksempel 2 D-6-methyl-8-8-(1-methylpropyl)aminoethylergolin-I-bishydrogenmaleinat.Example 2 D-6-methyl-8-8- (1-methylpropyl) aminoethylergoline I-bishydrogen malinate.
Til et opløsning af 0,27 g (1 mmol) D-6-methyl-8-f3-aminoethylergolin~ I i 15 ml methanol sættes 0,079 g (1,1 mmol) methylethylketon og 15 mg Adams-katalysator, og blandingen hydrogeneres under rystning og opvarmning til en temperatur på ca. 30-40°C med hydrogen under et overtryk på ca. 200 mm Hg, indtil den teoretiske hydrogenmængde er forbrugt. Efter afsluttet hydrogenering frafiltreres katalysatoren, og opløsningsmidlet afdampes under formindsket tryk. Resten (0,30 gTo a solution of 0.27 g (1 mmol) of D-6-methyl-8-β-aminoethylergoline-1 in 15 ml of methanol is added 0.079 g (1.1 mmol) of methyl ethyl ketone and 15 mg of Adams catalyst and the mixture is hydrogenated under shaking and heating to a temperature of approx. 30-40 ° C with hydrogen under an excess pressure of approx. 200 mm Hg until the theoretical amount of hydrogen is consumed. After hydrogenation is complete, the catalyst is filtered off and the solvent is evaporated under reduced pressure. The residue (0.30 g
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS745178A CS177530B1 (en) | 1974-07-19 | 1974-07-19 | New nbeta-substituted derivatives of b-beta-aminoethyl-ergoline-i their salts and methods for the production thereof |
| CS517874 | 1974-07-19 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK326475A DK326475A (en) | 1976-01-20 |
| DK143276B true DK143276B (en) | 1981-08-03 |
| DK143276C DK143276C (en) | 1981-11-30 |
Family
ID=5396167
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK326475A DK143276C (en) | 1974-07-19 | 1975-07-17 | ANALOGY PROCEDURE FOR THE PREPARATION OF N-BETA-SUBSTITUTED8-BETA-AMINOETHYLERGOLINE-I DERIVATIVES AND SALTS THEREOF |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4064130A (en) |
| JP (1) | JPS5134198A (en) |
| AT (1) | AT346502B (en) |
| BE (1) | BE831471A (en) |
| CA (1) | CA1050532A (en) |
| CS (1) | CS177530B1 (en) |
| DD (1) | DD121514A1 (en) |
| DE (1) | DE2532268A1 (en) |
| DK (1) | DK143276C (en) |
| FI (1) | FI59593C (en) |
| FR (1) | FR2278339A1 (en) |
| GB (1) | GB1500980A (en) |
| HU (1) | HU170509B (en) |
| NL (1) | NL7508692A (en) |
| SE (1) | SE7507911L (en) |
| SU (1) | SU632698A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS195905B1 (en) * | 1976-12-06 | 1980-02-29 | Milos Beran | 6-substituted derivatives of d-8-ergolin-i-ylacetic acid amide and process for preparing thereof |
| AU526764B2 (en) * | 1978-09-08 | 1983-01-27 | Farmitalia Carlo Erba S.P.A. | Ergoline derivatives |
| GB2120242A (en) * | 1982-04-30 | 1983-11-30 | Erba Farmitalia | Ergoline derivatives |
| JPS6130822U (en) * | 1984-07-30 | 1986-02-24 | 敬介 本多 | Underwater sensor |
| IT1243782B (en) * | 1990-08-06 | 1994-06-28 | Maria Francesca Devoto | COMPOSITION FOR THE CONTROL OF THE MULTIPLICATION OF VERTEBRATE ANIMALS BY MEANS OF FEED OR BAIT CONTAINING PERIPHERAL DOPAMINE AGONISTS |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA523781A (en) * | 1956-04-10 | Stoll Arthur | Compounds containing the lysergic acid skeleton, and the production thereof | |
| US3228942A (en) * | 1966-01-11 | Methyl and i,g-dimeti-iyl ergoline i compounds | ||
| DE1695752C3 (en) * | 1966-07-29 | 1974-06-06 | Societa Farmaceutici Italia, Mailand (Italien) | 1, ö-Dimethyl-ebeta-N-carbobenzoxyaminomethyl-2,3-dihydro-10alpha-ergoline and a process for its preparation |
| DE1910930A1 (en) * | 1968-03-07 | 1969-10-16 | Farmaceutici Italia | Process for the production of new 1,6-dimethyl-10alpha-ergoline derivatives |
| CH517762A (en) * | 1968-08-27 | 1972-01-15 | Spofa Vereinigte Pharma Werke | Process for the production of a new D-6-methylergoline derivative |
| NL7400790A (en) * | 1973-02-02 | 1974-08-06 | ||
| US3996228A (en) * | 1973-12-21 | 1976-12-07 | Societa' Farmaceutici Italia S.P.A. | Pyrimidinoaminoethyl ergoline derivatives |
| CS171480B1 (en) * | 1974-03-19 | 1976-10-29 |
-
1974
- 1974-07-19 CS CS745178A patent/CS177530B1/en unknown
-
1975
- 1975-07-10 AT AT533575A patent/AT346502B/en not_active IP Right Cessation
- 1975-07-10 SE SE7507911A patent/SE7507911L/en unknown
- 1975-07-15 HU HUSO1157A patent/HU170509B/hu unknown
- 1975-07-17 GB GB29966/75A patent/GB1500980A/en not_active Expired
- 1975-07-17 DK DK326475A patent/DK143276C/en not_active Application Discontinuation
- 1975-07-17 BE BE158389A patent/BE831471A/en unknown
- 1975-07-18 DE DE19752532268 patent/DE2532268A1/en not_active Withdrawn
- 1975-07-18 JP JP50087402A patent/JPS5134198A/en active Pending
- 1975-07-18 CA CA231,770A patent/CA1050532A/en not_active Expired
- 1975-07-18 US US05/597,389 patent/US4064130A/en not_active Expired - Lifetime
- 1975-07-18 FI FI752086A patent/FI59593C/en not_active IP Right Cessation
- 1975-07-18 DD DD187362A patent/DD121514A1/xx unknown
- 1975-07-18 SU SU752155222A patent/SU632698A1/en active
- 1975-07-21 NL NL7508692A patent/NL7508692A/en not_active Application Discontinuation
- 1975-07-21 FR FR7522725A patent/FR2278339A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| FI59593B (en) | 1981-05-29 |
| CA1050532A (en) | 1979-03-13 |
| DK326475A (en) | 1976-01-20 |
| FR2278339B1 (en) | 1979-08-10 |
| JPS5134198A (en) | 1976-03-23 |
| FR2278339A1 (en) | 1976-02-13 |
| BE831471A (en) | 1975-11-17 |
| DD121514A1 (en) | 1976-08-05 |
| ATA533575A (en) | 1978-03-15 |
| AU8314475A (en) | 1977-01-20 |
| HU170509B (en) | 1977-06-28 |
| NL7508692A (en) | 1976-01-21 |
| FI59593C (en) | 1981-09-10 |
| GB1500980A (en) | 1978-02-15 |
| US4064130A (en) | 1977-12-20 |
| FI752086A (en) | 1976-01-20 |
| DE2532268A1 (en) | 1976-02-05 |
| AT346502B (en) | 1978-11-10 |
| DK143276C (en) | 1981-11-30 |
| SU632698A1 (en) | 1978-11-15 |
| CS177530B1 (en) | 1977-07-29 |
| SE7507911L (en) | 1976-01-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AHB | Application shelved due to non-payment |